Schauer, Marianne, Kottek, Tina, Schönherr, Madeleine, Bhattacharya, Animesh, Ibrahim, Saleh M., Hirose, Misa, Köhling, Rüdiger, Fuellen, Georg, Schmitz, Ulf, and Kunz, Manfred (2015) A mutation in the NADH-dehydrogenase subunit 2 suppresses fibroblast aging. Oncotarget, 6. pp. 8552-8566.

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Abstract

Mutations of mitochondrial (mt)DNA cause a variety of human diseases and are implicated in premature aging syndromes. Here we investigated a single nucleotide exchange (leucine to methionine) at position nt4738 in the mitochondrial NADH dehydrogenase subunit 2 (Nd2) gene of the respiratory chain. Primary fibroblasts derived from the conplastic mouse strain C57BL/6J-mtALR/LTJ with mutant enzyme, possessed high enzyme activity and ATP production and low ROS production. Furthermore, Nd2-mutant fibroblasts expressed lower senescence markers. Transcriptome analysis revealed that the members of the p38MAPK pathway were significantly downregulated in Nd2-mutant mice. In agreement, inhibition of p38MAPK with SB203580 enhanced proliferation and reduced cytokine secretion in fibroblasts. In Nd2-mutant mouse skin, the amount of Ki67-positive cells was significantly higher than in control skin. The higher amount of Ki67-positive cells and the thicker epidermis in Nd2-mutant mice strongly supported the in vitro data. In conclusion, Nd2 is a mitochondrial gene, involved in age-related signaling pathways.

Item ID:	68995
Item Type:	Article (Research - C1)
ISSN:	1949-2553
Copyright Information:	Oncotarget applies the Creative Commons Attribution License (CC BY 4.0) to all works we publish (read the human-readable summary or the full license legal code). Under the CC BY 4.0, authors retain ownership of the copyright for their article, but authors allow anyone to download, reuse, reprint, modify, distribute, and/or copy articles in Oncotarget, so long as the original authors and source are cited.
Date Deposited:	19 Dec 2024 00:19
FoR Codes:	31 BIOLOGICAL SCIENCES > 3105 Genetics > 310502 Cell and nuclear division @ 100%
SEO Codes:	28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 100%
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